The objectives of this research are to determine the cellular basis for myeloid leukemia by first establishing the humoral regulators controlling normal granulocytes and macrophages, determining the cellular and biochemical mechanisms of action, then determining in what manner leukemic cells differ. To these ends, we have established that four glycoproteins GM-CSF, G-CSF, M-CSF and multi-CSF (IL-3) together control the production and differentiation of granulocytes and macrophages. Starting from mouse lung, L-cell or mitogen-stimulated lymphocyte-conditioned media, we have purified microgram amounts of each of these CSFs to homogeneity. We have, already, sequence data from GM-CSF and, with this, antigen probes will be synthesized for preparation of monoclonal antisera and cDNA probes for use in cloning the GM-CSF gene. It is proposed to carry out sequence analysis of the remaining three CSFs and attempt to clone their appropriate genes. G-CSF has been shown to suppress mouse myeloid leukemia cells and all four CSFs to activate the synthesis and/or phosphorylation of certain proteins in normal granulocyte-macrophage progenitor cells. The identity of these phosphoproteins with known oncogene-transforming proteins will be analyzed further to determine whether a common link exists in the mechanisms of action of regulatory glycoproteins and transforming viruses.